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Title: New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis
Contributor(s): Lee, Sang Hong  (author); Byrne, Enda M (author); Karlsson, Robert (author); Mattheisen, Manuel (author); Mattingsdal, Morten (author); McCarroll, Steven A (author); Medeiros, Helena (author); Melle, Ingrid (author); Milanova, Vihra (author); Myin-Germeys, Inez (author); Neale, Benjamin M (author); Ophoff, Roel A (author); Owen, Michael J (author); Mantzioris, Vasilis X (author); Pimm, Jonathan (author); Purcell, Shaun M (author); Puri, Vinay (author); Quested, Digby J (author); Rossin, Lizzy (author); Ruderfer, Douglas (author); Sanders, Alan R (author); Shi, Jianxin (author); Sklar, Pamela (author); St Clair, David (author); McGrath, John J (author); Stroup, T Scott (author); Van Os, Jim (author); Visscher, Peter M (author); Wiersma, Durk (author); Zammit, Stanley (author); Bridges, S Louis (author); Choi, Hyon K (author); Coenen, Marieke J H (author); de Vries, Niek (author); Dieude, Philippe (author); Mehta, Divya (author); Greenberg, Jeffrey D (author); Huizinga, Tom W J (author); Padyukov, Leonid (author); Siminovitch, Katherine A (author); Tak, Paul P (author); Worthington, Jane (author); De Jager, Philip L (author); Denny, Joshua C (author); Gregersen, Peter K (author); Klareskog, Lars (author); Stahl, Eli A (author); Mariette, Xavier (author); Plenge, Robert M (author); van Laar, Mart (author); van Riel, Piet (author); Zhao, Qiongyi (author); Kendler, Kenneth S (author); Sullivan, Patrick F (author); Price, Alkes L (author); O’Donovan, Michael (author); Hultman, Christina M (author); Okada, Yukinori (author); Mowry, Bryan J (author); Raychaudhuri, Soumya (author); Wray, Naomi R (author); Byerley, William (author); Cahn, Wiepke (author); Cantor, Rita M (author); Cichon, Sven (author); Cormican, Paul (author); Curtis, David (author); Kahler, Anna (author); Djurovic, Srdjan (author); Escott-Price, Valentina (author); Gejman, Pablo V (author); Georgieva, Lyudmila (author); Giegling, Ina (author); Hansen, Thomas F (author); Ingason, Andres (author); Kim, Yunjung (author); Konte, Bettina (author); Lee, Phil H (author); Vinkhuyzen, Anna A E (author); McIntosh, Andrew (author); McQuillin, Andrew (author); Morris, Derek W (author); Nothen, Markus M (author); O'Dushlaine, Colm (author); Olincy, Ann (author); Olsen, Line (author); Pato, Carlos N (author); Pato, Michele T (author); Pickard, Benjamin S (author); Ripke, Stephan (author); Posthuma, Danielle (author); Rasmussen, Henrik B (author); Rietschel, Marcella (author); Rujescu, Dan (author); Schulze, Thomas G (author); Silverman, Jeremy M (author); Thirumalai, Srinivasa (author); Werge, Thomas (author); Agartz, Ingrid (author); Amin, Farooq (author); Andreassen, Ole A (author); Azevedo, Maria H (author); Bass, Nicholas (author); Black, Donald W (author); Blackwood, Douglas H R (author); Bruggeman, Richard (author); Buccola, Nancy G (author); Choudhury, Khalid (author); Cloninger, C Robert (author); Corvin, Aiden (author); Craddock, Nicholas (author); Frisell, Thomas (author); Daly, Mark J (author); Datta, Susmita (author); Donohoe, Gary J (author); Duan, Jubao (author); Dudbridge, Frank (author); Fanous, Ayman (author); Freedman, Robert (author); Freimer, Nelson B (author); Friedl, Marion (author); Gill, Michael (author); Gusev, Alexander (author); Gurling, Hugh (author); De Haan, Lieuwe (author); Hamshere, Marian L (author); Hartmann, Annette M (author); Holmans, Peter A (author); Kahn, Rene S (author); Keller, Matthew C (author); Kenny, Elaine (author); Kirov, George K (author); Krabbendam, Lydia (author); Hu, Xinli (author); Krasucki, Robert (author); Lawrence, Jacob (author); Lencz, Todd (author); Levinson, Douglas F (author); Lieberman, Jeffrey A (author); Lin, Dan-Yu (author); Linszen, Don H (author); Magnusson, Patrik K E (author); Maier, Wolfgang (author); Malhotra, Anil K (author)
Publication Date: 2015
Open Access: Yes
DOI: 10.1093/ije/dyv136Open Access Link
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Abstract: Background: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. Methods: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. Results: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (−0.046, s.e. 0.026, P =0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (−0.174, s.e. 0.071, P =0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P =0.00090). Conclusions: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context.
Publication Type: Journal Article
Grant Details: NHMRC/APP1047956
Source of Publication: International Journal of Epidemiology, 44(5), p. 1706-1721
Publisher: Oxford University Press
Place of Publication: United Kingdom
ISSN: 1464-3685
Fields of Research (FoR) 2008: 060408 Genomics
060412 Quantitative Genetics (incl. Disease and Trait Mapping Genetics)
110999 Neurosciences not elsewhere classified
Fields of Research (FoR) 2020: 310509 Genomics
310506 Gene mapping
320999 Neurosciences not elsewhere classified
Socio-Economic Objective (SEO) 2008: 920110 Inherited Diseases (incl. Gene Therapy)
970106 Expanding Knowledge in the Biological Sciences
Socio-Economic Objective (SEO) 2020: 280102 Expanding knowledge in the biological sciences
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article

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